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用于治疗女性盆腔器官脱垂的纳米羟基磷灰石增强可吸收纳米纤维支架的体外和体内药物释放

In Vitro and In Vivo Drug Release from a Nano-Hydroxyapatite Reinforced Resorbable Nanofibrous Scaffold for Treating Female Pelvic Organ Prolapse.

作者信息

Chen Yi-Pin, Lo Tsia-Shu, Chien Yu-Han, Kuo Yi-Hua, Liu Shih-Jung

机构信息

Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung 20401, Taiwan.

School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.

出版信息

Polymers (Basel). 2024 Jun 12;16(12):1667. doi: 10.3390/polym16121667.


DOI:10.3390/polym16121667
PMID:38932015
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11207985/
Abstract

Pelvic prolapse stands as a substantial medical concern, notably impacting a significant segment of the population, predominantly women. This condition, characterized by the descent of pelvic organs, such as the uterus, bladder, or rectum, from their normal positions, can lead to a range of distressing symptoms, including pelvic pressure, urinary incontinence, and discomfort during intercourse. Clinical challenges abound in the treatment landscape of pelvic prolapse, stemming from its multifactorial etiology and the diverse array of symptoms experienced by affected individuals. Current treatment options, while offering relief to some extent, often fall short in addressing the full spectrum of symptoms and may pose risks of complications or recurrence. Consequently, there exists a palpable need for innovative solutions that can provide more effective, durable, and patient-tailored interventions for pelvic prolapse. We manufactured an integrated polycaprolactone (PCL) mesh, reinforced with nano-hydroxyapatite (nHA), along with drug-eluting poly(lactic-co-glycolic acid) (PLGA) nanofibers for a prolapse scaffold. This aims to offer a promising avenue for enhanced treatment outcomes and improved quality of life for individuals grappling with pelvic prolapse. Solution extrusion additive manufacturing and electrospinning methods were utilized to prepare the nHA filled PCL mesh and drug-incorporated PLGA nanofibers, respectively. The pharmaceuticals employed included metronidazole, ketorolac, bleomycin, and estrone. Properties of fabricated resorbable scaffolds were assessed. The in vitro release characteristics of various pharmaceuticals from the meshes/nanofibers were evaluated. Furthermore, the in vivo drug elution pattern was also estimated on a rat model. The empirical data show that nHA reinforced PCL mesh exhibited superior mechanical strength to virgin PCL mesh. Electrospun resorbable nanofibers possessed diameters ranging from 85 to 540 nm, and released effective metronidazole, ketorolac, bleomycin, and estradiol, respectively, for 9, 30, 3, and over 30 days in vitro. Further, the mesh/nanofiber scaffolds also liberated high drug levels at the target site for more than 28 days in vivo, while the drug concentrations in blood remained low. This discovery suggests that resorbable scaffold can serve as a viable option for treating female pelvic organ prolapse.

摘要

盆腔器官脱垂是一个重大的医学问题,尤其对相当一部分人群,主要是女性,产生显著影响。这种病症的特征是盆腔器官,如子宫、膀胱或直肠,从其正常位置下降,可导致一系列令人痛苦的症状,包括盆腔坠胀感、尿失禁以及性交时的不适。盆腔器官脱垂的治疗领域存在诸多临床挑战,这源于其多因素病因以及受影响个体所经历的各种不同症状。当前的治疗选择虽然在一定程度上能缓解症状,但往往难以解决所有症状,并且可能带来并发症或复发的风险。因此,迫切需要创新的解决方案,能够为盆腔器官脱垂提供更有效、持久且针对患者个体的干预措施。我们制造了一种用纳米羟基磷灰石(nHA)增强的聚己内酯(PCL)一体化网片,以及用于脱垂支架的载药聚乳酸 - 乙醇酸共聚物(PLGA)纳米纤维。这旨在为改善盆腔器官脱垂患者的治疗效果和生活质量提供一条有前景的途径。分别采用溶液挤出增材制造和电纺丝方法制备了填充nHA的PCL网片和载药的PLGA纳米纤维。所使用的药物包括甲硝唑、酮咯酸、博来霉素和雌酮。对制备的可吸收支架的性能进行了评估。评估了各种药物从网片/纳米纤维中的体外释放特性。此外,还在大鼠模型上估计了体内药物洗脱模式。实验数据表明,nHA增强的PCL网片比未改性的PCL网片具有更高的机械强度。电纺可吸收纳米纤维的直径范围为85至540纳米,体外分别有效释放甲硝唑、酮咯酸、博来霉素和雌二醇达9天、30天、3天和超过30天。此外,网片/纳米纤维支架在体内靶部位也能在超过28天的时间内释放高浓度药物,而血液中的药物浓度保持较低。这一发现表明,可吸收支架可作为治疗女性盆腔器官脱垂的一种可行选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/1443ed47e108/polymers-16-01667-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/161a6e381281/polymers-16-01667-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/92f751d20e43/polymers-16-01667-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/8563709ae4ad/polymers-16-01667-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/00a0946ad1bd/polymers-16-01667-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/dd34023f35e0/polymers-16-01667-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/3b9d72053eb4/polymers-16-01667-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/098017ce6a5e/polymers-16-01667-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/83b7eb9e9a53/polymers-16-01667-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/71b4160442bc/polymers-16-01667-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/6715b7b0749f/polymers-16-01667-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/df5fa4c10070/polymers-16-01667-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/4fd49d1183c3/polymers-16-01667-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/1443ed47e108/polymers-16-01667-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/161a6e381281/polymers-16-01667-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/92f751d20e43/polymers-16-01667-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/8563709ae4ad/polymers-16-01667-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/00a0946ad1bd/polymers-16-01667-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/dd34023f35e0/polymers-16-01667-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/3b9d72053eb4/polymers-16-01667-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/098017ce6a5e/polymers-16-01667-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/83b7eb9e9a53/polymers-16-01667-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/71b4160442bc/polymers-16-01667-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/6715b7b0749f/polymers-16-01667-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/df5fa4c10070/polymers-16-01667-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/4fd49d1183c3/polymers-16-01667-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50e/11207985/1443ed47e108/polymers-16-01667-g013.jpg

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Novel Bioresorbable Drug-Eluting Mesh Scaffold for Therapy of Muscle Injury.

ACS Biomater Sci Eng. 2024-4-8

[2]
Development of novel hybrid 3D-printed degradable artificial joints incorporating electrospun pharmaceutical- and growth factor-loaded nanofibers for small joint reconstruction.

Biomater Adv. 2024-5

[3]
Anti-Adhesive Resorbable Indomethacin/Bupivacaine-Eluting Nanofibers for Tendon Rupture Repair: In Vitro and In Vivo Studies.

Int J Mol Sci. 2023-11-12

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Comparative Effectiveness of Ketorolac Dosing Strategies for Emergency Department Patients With Acute Pain.

Ann Emerg Med. 2023-11

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Int Urogynecol J. 2023-6

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Polymers (Basel). 2021-10-29

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Fabrication of Drug-Eluting Polycaprolactone/poly(lactic--glycolic Acid) Prolapse Mats Using Solution-Extrusion 3D Printing and Coaxial Electrospinning Techniques.

Polymers (Basel). 2021-7-13

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Taiwan J Obstet Gynecol. 2021-3

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Polymers (Basel). 2021-1-20

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Codelivery of Sustainable Antimicrobial Agents and Platelet-Derived Growth Factor via Biodegradable Nanofibers for Repair of Diabetic Infectious Wounds.

ACS Infect Dis. 2020-10-9

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